4b6v | pdb_00004b6v

The third member of the eIF4E family represses gene expression via a novel mode of recognition of the methyl-7 guanosine cap moiety

spinqualitylabelsall models 4b6v Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4b6v is a 1 chain structure with sequence from Mus musculus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function IF4E3_MOUSE Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation of protein synthesis. May act as an inhibitor of EIF4E1 activity. Publication Abstract from PubMed Recognition of the methyl-7-guanosine (mG) cap structure on mRNA is an essential feature of mRNA metabolism and thus gene expression. Eukaryotic translation initiation factor 4E (eIF4E) promotes translation, mRNA export, proliferation, and oncogenic transformation dependent on this cap-binding activity. eIF4E-cap recognition is mediated via complementary charge interactions of the positively charged mG cap between the negative pi-electron clouds from two aromatic residues. Here, we demonstrate that a variant subfamily, eIF4E3, specifically binds the mG cap in the absence of an aromatic sandwich, using instead a different spatial arrangement of residues to provide the necessary electrostatic and van der Waals contacts. Contacts are much more extensive between eIF4E3-cap than other family members. Structural analyses of other cap-binding proteins indicate this recognition mode is atypical. We demonstrate that eIF4E3 relies on this cap-binding activity to act as a tumor suppressor, competing with the growth-promoting functions of eIF4E. In fact, reduced eIF4E3 in high eIF4E cancers suggests that eIF4E3 underlies a clinically relevant inhibitory mechanism that is lost in some malignancies. Taken together, there is more structural plasticity in cap recognition than previously thought, and this is physiologically relevant. eIF4E3 acts as a tumor suppressor by utilizing an atypical mode of methyl-7-guanosine cap recognition.,Osborne MJ, Volpon L, Kornblatt JA, Culjkovic-Kraljacic B, Baguet A, Borden KL Proc Natl Acad Sci U S A. 2013 Mar 5;110(10):3877-82. doi:, 10.1073/pnas.1216862110. Epub 2013 Feb 19. PMID:23431134 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Eukaryotic initiation factor 3D structures

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